Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond

TY - JOUR

T1 - Genetic susceptibility to type 2 diabetes and obesity

T2 - from genome-wide association studies to rare variants and beyond

AU - Grarup, Niels

AU - Sandholt, Camilla H

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2014/8

Y1 - 2014/8

N2 - During the past 7 years, genome-wide association studies have shed light on the contribution of common genomic variants to the genetic architecture of type 2 diabetes, obesity and related intermediate phenotypes. The discoveries have firmly established more than 175 genomic loci associated with these phenotypes. Despite the tight correlation between type 2 diabetes and obesity, these conditions do not appear to share a common genetic background, since they have few genetic risk loci in common. The recent genetic discoveries do however highlight specific details of the interplay between the pathogenesis of type 2 diabetes, insulin resistance and obesity. The focus is currently shifting towards investigations of data from targeted array-based genotyping and exome and genome sequencing to study the individual and combined effect of low-frequency and rare variants in metabolic disease. Here we review recent progress as regards the concepts, methodologies and derived outcomes of studies of the genetics of type 2 diabetes and obesity, and discuss avenues to be investigated in the future within this research field.

AB - During the past 7 years, genome-wide association studies have shed light on the contribution of common genomic variants to the genetic architecture of type 2 diabetes, obesity and related intermediate phenotypes. The discoveries have firmly established more than 175 genomic loci associated with these phenotypes. Despite the tight correlation between type 2 diabetes and obesity, these conditions do not appear to share a common genetic background, since they have few genetic risk loci in common. The recent genetic discoveries do however highlight specific details of the interplay between the pathogenesis of type 2 diabetes, insulin resistance and obesity. The focus is currently shifting towards investigations of data from targeted array-based genotyping and exome and genome sequencing to study the individual and combined effect of low-frequency and rare variants in metabolic disease. Here we review recent progress as regards the concepts, methodologies and derived outcomes of studies of the genetics of type 2 diabetes and obesity, and discuss avenues to be investigated in the future within this research field.

U2 - 10.1007/s00125-014-3270-4

DO - 10.1007/s00125-014-3270-4

M3 - Review

C2 - 24859358

SN - 0012-186X

VL - 57

SP - 1528

EP - 1541

JO - Diabetologia

JF - Diabetologia

IS - 8

ER -